Filters that discriminate based on size and/or shape are well known. One type of filter, for example, provides a tortuous path through which particles must navigate to pass through the filter. These are sometimes referred to as depth filters, and typically use a filter element made of a thick bed of fiber or other material. Due to their thickness and tortuous path filtration technique, these filters sometimes require relatively high transmembrane, i.e. transfilter, pressures to facilitate flow through the filter, due to its thickness and the tortuous path filtration technique.
In contrast to depth filters, another well-known type of filter employs relatively thin filter membranes, which typically have nominal pore sizes. Such membranes have been used in a wide variety of medical and industrial applications. For example, such filter membranes, with nominal pore size as low as 0.22 microns, have been used to filter bacteria and other matter from liquids, such as intravenous solutions. Such microporous filters also have been used to separate the cellular components of human blood (red cells, white cells and platelets) from liquid plasma in which the components are suspended. One well known device for carrying out such separation of blood components is the Autopheresis-C® separator, which is sold by Baxter Healthcare Corporation of Deerfield, Ill.
Although nominal pore size filter membranes have functioned generally satisfactorily, they tend to have limited porosity, discriminate principally on the basis of size alone, and sometimes suffer from reduced flow rates due to blockage on the surface of the membrane. “Porosity,” as used here, refers to the portion or percentage of the membrane surface made up of pores. This may also be referred to as the membrane “transparency.” A high porosity or transparency filter membrane, i.e., one in which a large portion of its surface is made up of pores, tends to allow higher flow rates through the filter membrane at a given transmembrane pressure than a low porosity or transparency membrane, i.e., one in which a small portion of its surface is made up of pores.
More recently, efforts have been directed to developing filter membranes having precise pore sizes and shapes for increased discrimination, particularly at the micron and sub-micron scale for the separation of, for example, cells and cell components. Such filters may have particular, but not exclusive, application in the separation of blood cells or other types of cells from one another or from the liquid (plasma in the case of blood cells) in which they are suspended.
Filters with micron or smaller scale pores, however, often have significant limitations. One such filter membrane is referred to as a “trac-etched” membrane. A trac-etched membrane has holes or pores of uniform micron-scale diameter for discrimination based on particle size. However, trac-etched membranes typically have low porosity, which limits the amount of throughput or filtration rates.
With trac-etched filters, for example, porosity tends to be between approximately two and six or seven percent. Attempts to increase porosity in trac-etched filter membranes often results in doublets or triplets, which are holes that overlap and therefore reduce the discrimination of the filter membrane. To avoid doublets or triplets, porosity in trac-etched membranes is typically limited to about seven percent and less.
In addition to low porosity, trac-etched membranes have another drawback. Trac-etched membranes have only circular pores and are therefore not suitable for discriminating based on non-circular particle shape.
More recently, it has been suggested to use lithographic microfabrication or similar micromachining techniques to provide filter membranes in which the pores have precise size and shape. U.S. Pat. No. 5,651,900 for example, discloses a particle filter made of inorganic material, such as silicon, that is suitable for use in high temperatures and with harsh solvents. The filter has precisely controlled pore sizes formed by interconnecting members, and has optional reinforcing ribs.
Precise pore size filter membranes have also been proposed, for example, for separating one class of blood cells from another. U.S. patent application Ser. No. 719,472, entitled “Method and Apparatus for Filtering Suspensions of Medical and Biological Fluids or the Like”, filed Sep. 25, 1996, and hereby incorporated by reference herein, describes such filter membranes having precise micron-scale and precision-shaped pores that can be used, for example, to separate red cells from white cells in human blood.
Experience has demonstrated, however, that the manufacture of microstructures, such as single-layer filter membranes by microlithography, micromachining or similar processes suffers from several constraints. As a “rule of thumb,” for example, the diameter or largest transverse dimension of the pores can be no smaller than about ½ or ⅓ the thickness of the membrane itself. Therefore, very small pore sizes, such as one micron or less, require very thin membranes of 2 to 3 microns or smaller in thickness. The inverse of this is commonly known as the “aspect ratio” and generally means that the thickness can be no more than about 2 or 3 times the pore size. Such very thin membranes, however, are typically very fragile and may not be sufficiently robust for some of the well known uses of microporous filter membranes.
One such well known use is in the Autopheresis-C® plasmapheresis device sold by Baxter Healthcare Corporation of Deerfield Ill. A detailed description of Autopheresis-C® device may be found in U.S. Pat. No. 5,194,145 to Schoendorfer, incorporated by reference herein. The Autopheresis-C® separator employs a microporous membrane mounted on a spinning rotor within a stationary housing. As described in the above patent, such a device is particularly efficient at separating blood cells from the plasma in which they are suspended. However, the microporous membrane used in such a device must be flexible and able to withstand the high rotational speeds, shear forces, and transmembrane pressures encountered in such a separation system.
As a result, microfabrication of microporous filter membranes has, in the past, been limited by competing considerations. On the one hand, finer filtration (smaller pore size) typically requires a filter membrane that is increasingly thin, and thus increasingly fragile. On the other hand, the desire for membrane robustness has generally been met by thicker membranes that do not typically permit the formation of high porosity very small, precisely controlled pores.
As one answer to the issue of membrane fragility, it has been proposed to provide a filter membrane in which the membrane layer is located on a support layer. U.S. Pat. No. 5,753,014 to Van Rijn describes a composite membrane having a polymeric membrane layer atop a separate polymeric macroporous support. The perforations or pores in the membrane layer and in the support are made by a micromachining process, such as a lithographic process in combination with etching. An intermediate layer may be deposited between the membrane and support for bonding enhancement and stress reduction. Although such a membrane may be suitable for some applications, it remains a relatively expensive membrane to fabricate, using small volume processes.
Very thin microporous membranes of micron-scale pores are also found in non-filtration applications. For example, published International Application No. WO 96/10966, published Apr. 18, 1996, discloses a microfabricated structure for implantation in host tissue. The structure was made up of a series of polyimide polymer membrane layers, each having a different geometric pattern of holes formed by a microfabrication technique. As a result of stacking these membranes together, a porous three-dimensional structure is created that promotes the growth of vascular structures in a host.
In any event, there remains a need for new or improved microporous filter membranes, for new or improved methods and processes for making such filter membranes, and for apparatus employing such membranes.